It has recently been recognized that some human retroviruses are capable of replicating in the central nervous system, and it is estimated that up to 80% of patients with diagnoses AIDS exhibit manifestations of CNS pathology. The pathogenesis of CNS diseases induced by retroviruses is not well understood. We are studying a murine retrovirus (WM-E) which was originally isolated from wild mice and has the capacity to cause a paralytic disease in some strains of laboratory mice with a latency of 12-20 weeks. The primary goals of this project are to identify the cells in the CNS in which this virus replicates and the mechanisms by which it causes motor neuron pathology. Using monoclonal antibodies specific for the gp70 of WM-E and nonreactive with that of endogenous viruses, we have localized sites of replication to spinal cord and brain stem. Viral antigen has been detected in endothelial cells and astrocytes as well as neurons. Murine retroviruses which do not cause neurological disease also infect the CNS. However, viral replication has only been detected in endothelial cells with no evidence of virus spread to the parenchyma. Thus, the capacity of WM-E to produce paralytic disease appears related to its capacity to spread from endothelial cells in the CNS to the parenchyma. In addition to the CNS, WM-E was also found to infect organs of external secretion. High titers of infectious virus were found in saliva, semen and uterine secretions. Horizontal transmission of this virus between adult mice occurred with high frequency, viremic males being the sole source of infection. Infectious virus was transferred to the female reproductive tract during copulation and was found within the oviducts associated with motile spermatozoa. Though saliva contained high concentrations of virus, oral transmission did not occur. The high efficiency of sexual transmission was associated with a unique tropism of WM-E for epithelial cells lining the epididymis. F-MuLV which was transmitted horizontally, but with low efficiency, did not replicate in these cells.